Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Bach Cuc Nguyen; Karine Lefort; Anna Mandinova; Dario Antonini; Vikram Devgan; Giusy Della Gatta; Maranke I. Koster; Zhuo Zhang; Jian Wang; Alice Tommasi Di Vignano; Jan Kitajewski; Giovanna Chiorino; Dennis R. Roop; Caterina Missero; G. Paolo Dotto

doi:10.1101/gad.1406006

Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Bach Cuc Nguyen, Karine Lefort, Anna Mandinova, Dario Antonini, Vikram Devgan, Giusy Della Gatta, Maranke I. Koster, Zhuo Zhang, Jian Wang, Alice Tommasi Di Vignano, Jan Kitajewski, Giovanna Chiorino, Dennis R. Roop, Caterina Missero, G. Paolo Dotto

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Abstract

Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.

Original language	English
Pages (from-to)	1028-1042
Number of pages	15
Journal	Genes and Development
Volume	20
Issue number	8
DOIs	https://doi.org/10.1101/gad.1406006
Publication status	Published - Apr 15 2006

Keywords

HES/HERP family members
Interferon-responsive genes
Keratinocyte
Notch
p63
Stem cells

ASJC Scopus subject areas

Genetics
Developmental Biology

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10.1101/gad.1406006

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Nguyen, B. C., Lefort, K., Mandinova, A., Antonini, D., Devgan, V., Gatta, G. D., Koster, M. I., Zhang, Z., Wang, J., Di Vignano, A. T., Kitajewski, J., Chiorino, G., Roop, D. R., Missero, C., & Dotto, G. P. (2006). Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation. Genes and Development, 20(8), 1028-1042. https://doi.org/10.1101/gad.1406006

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title = "Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation",

abstract = "Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.",

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author = "Nguyen, {Bach Cuc} and Karine Lefort and Anna Mandinova and Dario Antonini and Vikram Devgan and Gatta, {Giusy Della} and Koster, {Maranke I.} and Zhuo Zhang and Jian Wang and {Di Vignano}, {Alice Tommasi} and Jan Kitajewski and Giovanna Chiorino and Roop, {Dennis R.} and Caterina Missero and Dotto, {G. Paolo}",

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doi = "10.1101/gad.1406006",

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AU - Nguyen, Bach Cuc

AU - Lefort, Karine

AU - Mandinova, Anna

AU - Antonini, Dario

AU - Devgan, Vikram

AU - Gatta, Giusy Della

AU - Koster, Maranke I.

AU - Zhang, Zhuo

AU - Wang, Jian

AU - Di Vignano, Alice Tommasi

AU - Kitajewski, Jan

AU - Chiorino, Giovanna

AU - Roop, Dennis R.

AU - Missero, Caterina

AU - Dotto, G. Paolo

PY - 2006/4/15

Y1 - 2006/4/15

N2 - Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.

AB - Notch signaling promotes commitment of keratinocytes to differentiation and suppresses tumorigenesis. p63, a p53 family member, has been implicated in establishment of the keratinocyte cell fate and/or maintenance of epithelial self-renewal. Here we show that p63 expression is suppressed by Notch1 activation in both mouse and human keratinocytes through a mechanism independent of cell cycle withdrawal and requiring down-modulation of selected interferon-responsive genes, including IRF7 and/or IRF3. In turn, elevated p63 expression counteracts the ability of Notch1 to restrict growth and promote differentiation. p63 functions as a selective modulator of Notch1-dependent transcription and function, with the Hes-1 gene as one of its direct negative targets. Thus, a complex cross-talk between Notch and p63 is involved in the balance between keratinocyte self-renewal and differentiation.

KW - HES/HERP family members

KW - Interferon-responsive genes

KW - Keratinocyte

KW - Notch

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KW - Stem cells

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Cross-regulation between Notch and p63 in keratinocyte commitment to differentiation

Abstract

Keywords

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